Digital Commons Network^™

G9a Is Essential For Emt-Mediated Metastasis And Maintenance Of Cancer Stem Cell-Like Characters In Head And Neck Squamous Cell Carcinoma, Shuli Liu, Dongxia Ye, Wenzheng Guo, Wenwen Yu, Yue He, Jingzhou Hu, Yanan Wang, Ling Zhang, Yueling Liao, Hongyong Song, Shuangshuang Zhong, Dongliang Xu, Huijing Yin, Beibei Sun, Xiaofei Wang, Jingyi Liu, Yadi Wu, Binhua P. Zhou, Zhiyuan Zhang, Jiong Deng

Markey Cancer Center Faculty Publications

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 …

Medical Students In Microscopic Anatomy And Pathology Laboratories: Design Of An E-Learning Histology And Histopathology Atlas As An Evolving Response To Interdisciplinary Pre-Clinical Curricular Needs, Michelle S. Davis, Alexandra Mills, Gisela Butera, Donald S. Karcher, Patricia S. Latham, Janette Krum, Rosalyn A. Jurjus

Anatomy and Regenerative Biology Faculty Publications

E-learning, also known as computer-assisted learning, successfully bridges anatomical knowledge and transferrable skills, such as critical analysis, teamwork, leadership and communication. Several institutions have already integrated histology and physiology in team based laboratory approaches, but integration of histology and pathology instruction has been done to a lesser extent. Our aim was to develop an e-learning atlas that integrates microanatomy and pathology laboratory for an interdisciplinary pre-clinical medical curriculum.

A multidisciplinary team of teaching faculty and students developed an online atlas (microanatomyatlas.com) that includes a library of histology and histopathology images. Traditional laboratory manual instructions and study objectives were added onto …

Ppm1a Regulates Antiviral Signaling By Antagonizing Tbk1-Mediated Sting Phosphorylation And Aggregation, Zexing Li, Ge Liu, Liwei Sun, Yan Teng, Xuejiang Guo, Jianhang Jia, Jiahao Sha, Xiao Yang, Dahua Chen, Qinmiao Sun

Markey Cancer Center Faculty Publications

Stimulator of interferon genes (STING, also known as MITA and ERIS) is critical in protecting the host against DNA pathogen invasion. However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting STING in its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro. Importantly, we provide evidence that whereas TBK1 promotes STING aggregation in a phosphorylation-dependent manner, PPM1A antagonizes STING aggregation by dephosphorylating both STING and TBK1, emphasizing that phosphorylation is crucial for the efficient activation of STING. Our …

Maternal Analgosedation And Breastfeeding: Guidance For The Pediatrician, Karel Allegaert, Johannes N. Van Den Anker

Surgery Faculty Publications

As part of analgosedative treatment modalities after delivery (e.g. caesarean related pain, birth related trauma, pre-existing pain syndromes), mothers are treated with different analgosedatives that may also affect the nursing infant. This review aims to summarize the available knowledge on commonly prescribed analgosedatives (opioids, intravenous and inhalational anesthetics, benzodiazepines, non-opioid analgesics, and local anesthetics) during breastfeeding.

We propose that the use of systemic non-opioid analgesics, local anesthetics, inhalational or intravenous anesthetics is safe when mothers are nursing. When systemic opioids are used, we recommend pediatricians to consider clinical monitoring of the infant for sedation. The duration of maternal exposure ( …

Metformin Prevents Aggressive Ovarian Cancer Growth Driven By High-Energy Diet: Similarity With Calorie Restriction, Zaid Al-Wahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Robert T. Morris, Rouba Ali-Fehmi, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan

Department of Obstetrics and Gynecology Research Publications

Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking …

Ocular Complications Of Inflammatory Bowel Disease, Rana Mady, Will Grover, Salim Butrus

Ophthalmology Faculty Publications

No abstract provided.

The Flavonoid Nobiletin Inhibits Tumor Growth And Angiogenesis Of Ovarian Cancers Via The Akt Pathway, Jianchu Chen, Allen Y. Chen, Haizhi Huang, Xingqian Ye, William D. Rollyson, Haley E. Perry, Kathleen C. Brown, Yon Rojanasakul, Gary O. Rankin, Piyali Dasgupta, Yi Charlie Chen

Pharmaceutical Science and Research

Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving …

Biological Response To Prosthetic Debris., Diana Bitar, Javad Parvizi

Rothman Institute Papers

Joint arthroplasty had revolutionized the outcome of orthopaedic surgery. Extensive and collaborative work of many innovator surgeons had led to the development of durable bearing surfaces, yet no single material is considered absolutely perfect. Generation of wear debris from any part of the prosthesis is unavoidable. Implant loosening secondary to osteolysis is the most common mode of failure of arthroplasty. Osteolysis is the resultant of complex contribution of the generated wear debris and the mechanical instability of the prosthetic components. Roughly speaking, all orthopedic biomaterials may induce a universal biologic host response to generated wear débris with little specific characteristics …

Nasolacrimal System Aeration On Computed Tomographic Imaging: Effects Of Patient Positioning And Scan Orientation., Craig N Czyz, Thomas S Bacon, Andrew W Stacey, Eva N Cahill, Bryan R Costin, Boris I Karanfilov, Kenneth V Cahill

Ambulatory and Primary Care Articles

PURPOSE: To determine the impact of patient positioning and scan orientation on the appearance of air in the nasolacrimal drainage system on computed tomography (CT) imaging, and the repeatability of the observations.

METHODS: This was a retrospective analysis of CT images for 92 patients.

RESULTS: Air was found to be present more fully in the upright-position group as compared with the supine-position group. Comparing axial and coronal scan orientation, no difference in aeration was found, except for the nasolacrimal duct in the upright-position group.

CONCLUSION: Patient position should be accounted for in diagnostic conclusions and treatment decisions based on CT.

Targeting Tumor-Initiating Cells: Eliminating Anabolic Cancer Stem Cells With Inhibitors Of Protein Synthesis Or By Mimicking Caloric Restriction., Rebecca Lamb, Hannah Harrison, Duncan L Smith, Paul A Townsend, Thomas Jackson, Bela Ozsvari, Ubaldo E. Martinez-Outshoorn, Md, Richard Pestell, Anthony Howell, Michael P. Lisanti, Federica Sotgia

Kimmel Cancer Center Faculty Papers

We have used an unbiased proteomic profiling strategy to identify new potential therapeutic targets in tumor-initiating cells (TICs), a.k.a., cancer stem cells (CSCs). Towards this end, the proteomes of mammospheres from two breast cancer cell lines were directly compared to attached monolayer cells. This allowed us to identify proteins that were highly over-expressed in CSCs and/or progenitor cells. We focused on ribosomal proteins and protein folding chaperones, since they were markedly over-expressed in mammospheres. Overall, we identified >80 molecules specifically associated with protein synthesis that were commonly upregulated in mammospheres. Most of these proteins were also transcriptionally upregulated in human …

Posterior Surgical Approach Procedures For Cervical Myelopathy, Pedro H.I. Pohl, Marcel Jun Tamaoki, Luciano M. Rodrigues, Kristen Radcliff, Takashi Yurube, James D. Kang, João Carlos Belloti

Department of Orthopaedic Surgery Faculty Papers

This is the protocol for a review and there is no abstract. The objectives are as follows: The main objective of this review is to assess the effects of laminectomy and fusion versus laminoplasty for multilevel cervical stenosis with myelopathy, on treatment outcomes such as pain, quality of life, functional and neurological improvement, and complication rates. © 2015 The Cochrane Collaboration.

Unlocking The Mysteries Of Tdp-43, Keith A. Josephs, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Is Metabolic Syndrome Predictive Of Prevalence, Extent, And Risk Of Coronary Artery Disease Beyond Its Components? Results From The Multinational Coronary Ct Angiography Evaluation For Clinical Outcome: An International Multicenter Registry (Confirm), Ricardo Cury

All Publications

No abstract provided.

Metabolic Reprogramming Of Cancer-Associated Fibroblasts By Idh3Α Downregulation, Daoxiang Zhang, Yongbin Wang, Zhimin Shi, Jingyi Liu, Pan Sun, Xiaodan Hou, Jian Zhang, Shimin Zhao, Binhua P. Zhou, Jun Mi

Markey Cancer Center Faculty Publications

Cancer-associated fibroblasts (CAFs) provide critical metabolites for tumor growth and undergo metabolic reprogramming to support glycolysis. However, the molecular mechanisms responsible for this change remain unclear. Here, we report that TGF-β1- or PDGF-induced CAFs switch from oxidative phosphorylation to aerobic glycolysis. We identify downregulation of isocitrate dehydrogenase 3α (IDH3α) as a marker for this switch. Furthermore, miR-424 downregulates IDH3α during CAF formation. Downregulation of IDH3α decreases the effective level of α-ketoglutarate (α-KG) by reducing the ratio of α-KG to fumarate and succinate, resulting in PHD2 inhibition and HIF-1α protein stabilization. The accumulation of HIF-1α, in turn, promotes glycolysis by increasing …

Brain Blast 2015 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2015 listing the expected presenters at this event.*

Hospice Home Immersion Project: Advancing Medical Education, Marilyn R. Gugliucci, Himanshu Malhotra, Andrea Gaul

Geriatric Medicine Faculty Publications

The University of New England College of Osteopathic Medicine (UNECOM) Hospice Immersion project was piloted in 2014 in southern Maine. It was designed and implemented as an experiential medical education learning model whereby medical students were “admitted” into the local Hospice Home to live there for 48 hours. Until this project, palliative and end of life care education at US Medical Schools and specifically UNECOM were accomplished through traditional medical education methods. The Hospice Immersion project utilizes qualitative ethnographic and autobiographic research designs, whereby a unique environment or “culture” (Hospice Home) is observed and life experiences of the medical student …

The Land Of Opportunities For Research On Rare Genetic Neurological Disorders, Muhammad Ulusyar Khan, Fazal M. Arain

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Labrad : Vol 41, Issue 1 - March 2015, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• An Overview of Proficiency Testing
• Sources of Pre-analytical Variations
• Five Q-Framework for Implementing Total Quality Management in Laboratory
• Delta Check in Clinical Laboratory
• Indicators of Quality Improvement in Surgical Pathology
• Types of Analytical Errors
• Method Validation for Quantitative Tests: CAP Recommendations
• Levey Jenning Chart and a Guide to Use Westgard Rules
• Quality Control of Vitek-2 System
• Establishing Quality Control Values for Haematology Parameters

Oncolog, Volume 60, Number 03, March 2015, Bryan Tutt, Kathryn L. Hale, K. Stuyck

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Small Cell Lung Cancer Studies May Increase Treatment Options: Despite advances in treating many cancers, the standard treatment of small cell lung cancer has remained unchanged for decades. But researchers at The University of Texas MD Anderson Cancer Center are exploring several new approaches to treat small cell lung cancer.
• Improved Maintenance Therapy Promotes Myeloma patients' Quality of Life After Stem Cell Transplantation: High-dose chemotherapy followed by autologous stem cell transplantation can prolong survival for patients with multiple myeloma. However, patients remain at a high risk of relapse even after transplantation. Maintenance therapy can extend remission in these patients, and …

Digest Of The Philadelphia College Of Osteopathic Medicine (Spring 2015), Philadelphia College Of Osteopathic Medicine

Digest

The Spring 2015 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Message from the President
• PCOM Updates
• Development News
• Institutional Announcement: Farewell to Paul W. McGloin, CPA, LLD (Hon.)
• Institutional Heritage: Founders’ Day 2015
• Feature: The Healing Touch – Health Advocacy without Borders
• Bringing Hope and Care to Ukrainians – Zenia Chernyk, DO ’77
• Helping Victims of Human Trafficking in India – Winson T. George, PhD, DO ’09
• Hands-on in Haiti – Shelly Chvotzkin, DO ’02
• Class Notes
• My Turn

Mortality Patterns Among Critically Ill Children In A Pediatric Intensive Care Unit Of A Developing Country, Naveed-Ur-Rehman Siddiqui, Zohaib Ashraf, Humaira Jurair, Anwarul Haque

Department of Paediatrics and Child Health

Background and Aim: Advances in biomedical technology have made medical treatment to be continued beyond a point, at which it does not confer an advantage but may increase the suffering of patients. In such cases, continuation of care may not always be useful, and this has given rise to the concept of limitation of life-sustaining treatment. Our aim was to study mortality patterns over a 6-year period in a Pediatric Intensive Care Unit (PICU) in a developing country and to compare the results with published data from other countries.
Materials and Methods: Retrospective cohort study was conducted in a PICU …

Macular Pigment Optical Density Is Lower In Type 2 Diabetes, Compared With Type 1 Diabetes And Normal Controls., James Loughman, Grainne Scanlon, Paul Connell, Audrey Murphy, Karen O'Conner, Mathew Ratzlaff, Brittany Foerg

Articles

Purpose: This study was designed to investigate the optical density of macular pigment in Type 1 and Type 2 diabetes subjects relative to normal controls

Mitochondria-Associated Micrornas In Rat Hippocampus Following Traumatic Brain Injury, Wang-Xia Wang, Nishant P. Visavadiya, Jignesh D. Pandya, Peter T. Nelson, Patrick G. Sullivan, Joe E. Springer

Sanders-Brown Center on Aging Faculty Publications

Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediators of neuronal development, synaptic plasticity, and neurodegeneration. Several miRNAs show altered expression following TBI; however, the …

Characterization Of Genomic Variations In Snps Of Pe_Pgrs Genes Reveals Deletions And Insertions In Extensively Drug Resistant (Xdr) M. Tuberculosis Strains From Pakistan., Akber Kanji, Zahra Hasan, Ruth Mcnerney, Mridul Nair, Asho Ali, Kim Mallard, Taane G. Clark, Ambreen Zaver, Sana Jafri,, Rumina Hasan

Department of Pathology and Laboratory Medicine

BACKGROUND:

Mycobacterium tuberculosis (MTB) PE_PGRS genes belong to the PE multigene family. Although the function of PE_PGRS genes is unknown, it is hypothesized that the PE_PGRS genes may be associated with antigenic variability in MTB.

MATERIAL AND METHODS:

Whole genome sequencing analysis was performed on (n=37) extensively drug-resistant (XDR) MTB strains from Pakistan, which included Lineage 1 (East African Indian, n=2); Other lineage 1 (n=3); Lineage 3 (Central Asian, n=24); Other lineage 3 (n=4); Lineage 4 (X3, n=1) and T group (n=3) MTB strains.

RESULTS:

There were 107 SNPs identified from the analysis of 42 PE_PGRS genes; of these, 13 …

The Association Of Cognitive Endophenotypes And Risky Single Nucleotide Polymorphisms Of Alzheimer's Disease Within The Alzheimer's Disease Neuroimaging Initiative (Adni) Database, Kyle Joseph Jennette

USF Tampa Graduate Theses and Dissertations

Objective: The purpose of this study was to assess the influence of three single nucleotide polymorphisms (SNP) previously associated with Alzheimer's disease on specific domains of cognition, when controlling for Apolipoprotein E gene (APOE), in a sample of individuals with Alzheimer's disease. Methods: The data were drawn from the Alzheimer's Disease Neuroimaging Initiative database, a comprehensive, longitudinal database of controls, persons with mild cognitive impairment, and persons with mild Alzheimer's disease. Each subject has a full neuropsychological assessment, neuroimaging, genetic sequencing, and physical evaluation. For the purposes of this study, individuals were selected based on the presence of the three …

Inhibition Of Inos As A Novel Effective Targeted Therapy Against Triple-Negative Breast Cancer, Sergio Granados-Principal, Yi Liu, Maria L. Guevara, Elvin Blanco, Dong Soon Choi, Wei Qian, Tejal Patel, Angel A. Rodriguez, Joseph Cusimano, Heidi L. Weiss, Hong Zhao, Melissa D. Landis, Bhuvanesh Dave, Steven S. Gross, Jenny C. Chang

Markey Cancer Center Faculty Publications

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors.

METHODS: iNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors …

Antibiotics For Cancer Therapy., Richard Pestell, Albert A Rizvanov

Department of Cancer Biology Faculty Papers

No abstract provided.

Is 2015 The Primetime Year For Prehypertension? Prehypertension: A Cardiovascular Risk Factor Or Simply A Risk Marker?, Gabriel B. Habib, Salim S. Virani, Hani Jneid

Office of the Provost

No abstract provided.

Toll Like Receptor (Tlr) Stimulation For Ocular Angiogenesis And Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of stimulators of the TLR3 and TLR7 receptors, Trif or of IL-10 and IL-12 inhibits ocular angiogenesis. Furthermore, all siRNAs (both targeted and non-targeted) can inhibit ocular angiogenesis.

Mdr1 Sirna Loaded Hyaluronic Acid-Based Cd44 Targeted Nanoparticle Systems Circumvent Paclitaxel Resistance In Ovarian Cancer, Xiaoqian Yang, Arun K. Iyer, Amit Singh, Edwin Choy, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of …